This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer of the upper aerodigestive tract is inextricably linked to the combined effect of chronic tobacco and alcohol use. Laryngeal cancer is very rare in nonsmokers, and the risk increases with numbers of cigarettes smoked per day. Approximately 15,000 laryngeal cancers are diagnosed each year, representing about 1.2% of all newly diagnosed cancers. Greater awareness of the signs and symptoms of laryngeal cancer by primary care physicians over the past decade has led to earlier diagnosis of laryngeal cancer, which presents quite subtly at earlier stages, with the cardinal symptom being voice change, specifically hoarseness. Since early diagnosis of laryngeal cancer results in a much higher cure rate (>90%) than late-stage disease (<60%), clinicians are aggressive with respect to obtaining vocal cord biopsies, even though this means many biopsies will yield a diagnosis that is not cancer. Vocal cord biopsy is not innocuous, and frequently leads to irreversible dysphonia and hoarseness as a consequence of removing the delicate viscoelastic connective tissues. Invasive laryngeal cancer is defined as the spread of vocal cancer into this same tissue. Diagnosing the presence or high likelihood of an invasive laryngeal tumor without biopsy would provide surgeons with the ability to better determine which patients are candidates for surgical endoscopy and biopsy. Likewise, many patients may be spared the morbidity associated with a vocal cord biopsy. An office-based, non-contact technique is needed to obtain real-time cross-sectional images of the vocal cord microstructure and hence aid in distinguishing invasive from non-invasive tumors. Such a device would allow relatively simple diagnostic screening of patients at high risk of or suspected as having laryngeal cancer and would allow evaluation of chronic laryngeal disease related to second-hand tobacco smoke exposure. We propose to accomplish this task by developing an advanced Optical Coherence Tomography (OCT)-based instrument to image the larynx in the office without the need for anesthesia or sedation. OCT is an emerging optical imaging modality that uses light to produce crosssectional images in tissue, which under we have pioneered use in more than 300 patients to image the upper aero-digestive tract in operative settings. The proposed research will design and develop OCT probes that will work in tandem with existing conventional office-based laryngeal endoscopy systems. We believe use of this emerging technology will ultimately 1) provide a means to screen patients for early laryngeal cancer and minimize the number of unnecessary biopsies performed to diagnose early laryngeal cancer, thus reducing iatrogenic dysphonia;2) guide otolaryngologists during microsurgery to focus biopsies on regions with a higher probability of microinvasive cancer;and 3) allow archival storage of cross-sectional images of the vocal cord which can be used to determine changes in cord microanatomy and structure over time, augmenting conventional static two-dimensional laryngeal photographs. We firmly believe OCT has the potential to become as vital as CT and MRI for managing head and neck malignancies since it provides such exquisite detail on tissue microstructure;unlike these traditional imaging modalities, performing laryngeal OCT imaging in the office remains a major technical challenge, and therefore is now the main focus of our research. Our proposal is clinically driven and focuses bringing an advanced laryngeal imaging device into clinical practice and large scale evaluation. The technical challenges in device design lie at the nexus of medicine, surgery, and biomedical engineering. The specific aims are 1. Design and construct OCT probe that can be integrated with an office-based laryngeal endoscopy imaging system. 2. Perform large-scale screening of patients at risk of laryngeal cancer, and correlate F-OCT images with clinical findings and conventional video endoscopic images. 3. Correlate OCT vocal cord images with biopsies in the subset of patients undergoing microlaryngeal surgery for cancer diagnosis.